A reappraisal of transcriptional regulation by NR5A1 and beta-catenin in adrenocortical carcinoma DOI Creative Commons
Enzo Lalli

Frontiers in Endocrinology, Journal Year: 2023, Volume and Issue: 14

Published: Dec. 8, 2023

Background Overexpression of the transcription factor NR5A1 and constitutive activation canonical Wnt signalling leading to nuclear translocation beta-catenin are hallmarks malignancy in adrenocortical carcinoma (ACC). Based on analysis genomic profiles H295R ACC cells, Mohan et al. ( Cancer Res . 2023; 83: 2123-2141) recently suggested that a major determinant driving proliferation differentiation malignant is interaction chromatin regulate gene expression. Methods I reanalyzed same set data generated by other published knockdown-validated target genes, Results Beta-catenin mainly found association T cell factor/lymphoid enhancer (TCF/LEF) motifs DNA. distinct sets cells. Conclusion Overall, my suggests model where overexpression principally act independently, rather than functionally interacting, drive malignancy.

Language: Английский

Nuclear Phosphoinositides as Key Determinants of Nuclear Functions DOI Creative Commons
Magdalena Castellano Vidalle, Bhavwanti Sheth, Antonietta Fazio

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(7), P. 1049 - 1049

Published: June 28, 2023

Polyphosphoinositides (PPIns) are signalling messengers representing less than five per cent of the total phospholipid concentration within cell. Despite their low concentration, these lipids critical regulators various cellular processes, including cell cycle, differentiation, gene transcription, apoptosis and motility. PPIns generated by phosphorylation inositol head group phosphatidylinositol (PtdIns). Different pools found at distinct subcellular compartments, which regulated an array kinases, phosphatases phospholipases. Six seven species have been in nucleus, nuclear envelope, nucleoplasm nucleolus. The identification characterisation interactor effector proteins nucleus led to increasing interest role signalling. However, regulation functions complex still being elucidated. This review summarises our current understanding localisation, biogenesis physiological different nucleus.

Language: Английский

Citations

13
Investigation of Flavonoid Scaffolds as DAX1 Inhibitors against Ewing Sarcoma through Pharmacoinformatic and Dynamic Simulation Studies DOI Open Access
Muhammad Yasir, Jin‐Young Park,

Eun‐Taek Han

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(11), P. 9332 - 9332

Published: May 26, 2023

Dosage-sensitive sex reversal, adrenal hypoplasia critical region, on chromosome X, gene 1 (DAX1) is an orphan nuclear receptor encoded by the NR0B1 gene. The functional study showed that DAX1 a physiologically significant target for EWS/FLI1-mediated oncogenesis, particularly Ewing Sarcoma (ES). In this study, three-dimensional structure was modeled employing homology modeling approach. Furthermore, network analysis of genes involved in also carried out to evaluate association and other with ES. Moreover, molecular docking check binding profile screened flavonoid compounds against DAX1. Therefore, 132 flavonoids were docked predicted active pocket pharmacogenomics performed top ten ES-related clusters. As result, five best flavonoid-docked complexes selected further evaluated Molecular Dynamics (MD) simulation studies at 100 ns. MD trajectories generating RMSD, hydrogen bond plot analysis, interaction energy graphs. Our results demonstrate interactive profiles region can be used as potential therapeutic agents DAX1-mediated augmentation ES after in-vitro in-vivo evaluations.

Language: Английский

Citations

11
Nuclear Phospholipids and Signaling: An Update of the Story DOI Creative Commons
Irene Casalin, Eleonora Ceneri, Stefano Ratti

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(8), P. 713 - 713

Published: April 19, 2024

In the last three decades, presence of phospholipids in nucleus has been shown and thoroughly investigated. A considerable amount interest raised about nuclear inositol lipids, mainly because their role signaling acting. Here, we review main issues phospholipid localization lipids related enzymes cellular signaling, both physiological pathological conditions.

Language: Английский

Citations

4
Update on Adrenocortical Carcinoma DOI

Zahra Sarrafan-Chaharsoughi,

Pouria Yazdian Anari, Ashkan A. Malayeri

et al.

Urologic Clinics of North America, Journal Year: 2025, Volume and Issue: 52(2), P. 275 - 286

Published: March 13, 2025

Language: Английский

Citations

0
Targeting pediatric adrenocortical carcinoma: Molecular insights and emerging therapeutic strategies DOI Creative Commons
Michaela Kuhlen, Maximilian Schmutz, Marina Kunstreich

et al.

Cancer Treatment Reviews, Journal Year: 2025, Volume and Issue: 136, P. 102942 - 102942

Published: April 17, 2025

Language: Английский

Citations

0
FSCN1 as a new druggable target in adrenocortical carcinoma DOI Creative Commons
Carmen Ruggiero, Mariangela Tamburello, Elisa Rossini

et al.

International Journal of Cancer, Journal Year: 2023, Volume and Issue: 153(1), P. 210 - 223

Published: March 27, 2023

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with high risk of relapse and metastatic spread. The actin-bundling protein fascin (FSCN1) overexpressed in aggressive ACC represents reliable prognostic indicator. FSCN1 has been shown to synergize VAV2, guanine nucleotide exchange factor for the Rho/Rac GTPase family, enhance invasion properties cancer cells. Based on those results, we investigated effects inactivation by CRISPR/Cas9 or pharmacological blockade invasive cells, both vitro an vivo zebrafish model. Here, showed that transcriptional target β-catenin H295R cells its resulted defects cell attachment proliferation. knock-out modulated expression genes involved cytoskeleton dynamics adhesion. When Steroidogenic Factor-1 (SF-1) dosage was upregulated activating their capacities, reduced number filopodia, lamellipodia/ruffles focal adhesions, while decreasing Matrigel. Similar were produced inhibitor G2-044, which also diminished other lines expressing lower levels than H295R. In model, metastases formation significantly G2-044 formed Our results indicate new druggable provide rationale future clinical trials inhibitors patients ACC.

Language: Английский

Citations

10
Nuclear Phospholipids and Signaling: An Update of the Story DOI Open Access
Irene Casalin, Eleonora Ceneri, Stefano Ratti

et al.

Published: March 28, 2024

In the last three decades presence of phospholipids in nucleus has been shown and thoroughly investigated. A great interest raised about nuclear inositol lipids mainly because their role signalling acting. Here we review main issues phospholipid localization related enzymes cellular signaling both physiological pathological conditions.

Language: Английский

Citations

1
Comprehensive Review of Biological Functions and Therapeutic Potential of Perilla Seed Meal Proteins and Peptides DOI Creative Commons
Y. Hu,

Huan Luo,

Vasudeva Reddy Netala

et al.

Foods, Journal Year: 2024, Volume and Issue: 14(1), P. 47 - 47

Published: Dec. 27, 2024

This comprehensive review explores the biological functions of Perilla frutescens seed proteins and peptides, highlighting their significant potential for health therapeutic applications. delves into mechanisms through which perilla peptides combat oxidative stress protect cells from damage, encompassing free radical scavenging, metal chelating, in vivo antioxidant, cytoprotective activities. exhibit robust anti-aging properties by activating Nrf2 pathway, enhancing cellular antioxidant capacity, supporting skin promotion keratinocyte growth, maintenance collagen integrity, reduction senescent cells. Additionally, they demonstrate antidiabetic activity inhibiting α-amylase α-glucosidase. The cardioprotective effects are underscored ACE-inhibitory activities enhanced defenses. Further, contribute to improved gut beneficial flora reinforcing intestinal barriers. In liver, kidney, testicular health, reduce apoptotic damage while normalizing electrolyte levels protecting against cyclophosphamide-induced reproductive endocrine disruptions restoring hormone synthesis. Promising anticancer is also demonstrated inhibition key cancer cell lines, alongside anti-inflammatory immunomodulating Their anti-fatigue enhance exercise performance muscle function, peptide nanoparticles show targeted drug delivery. diverse applications support as functional food additives agents.

Language: Английский

Citations

1
Steroidogenic Factor-1 form and function: From phospholipids to physiology DOI Creative Commons

Alexis Campbell,

Woong Jae Choi, S. Ethan

et al.

Advances in Biological Regulation, Journal Year: 2023, Volume and Issue: 91, P. 100991 - 100991

Published: Sept. 27, 2023

Language: Английский

Citations

3
Transgenerational inheritance of adrenal steroidogenesis inhibition induced by prenatal dexamethasone exposure and its intrauterine mechanism DOI Creative Commons
Zheng He, Jinzhi Zhang, Ya‐Wen Chen

et al.

Cell Communication and Signaling, Journal Year: 2023, Volume and Issue: 21(1)

Published: Oct. 18, 2023

Abstract Background Adrenal gland is the synthesis and secretion organ of glucocorticoid, which crucial to fetal development postnatal fate. Recently, we found that prenatal dexamethasone exposure (PDE) could cause adrenal dysfunction in offspring rats, but its multigenerational genetic effects related mechanisms have not been reported. Methods The PDE rat model was established, female filial generation 1 (F1) rats mate with wild males produce F2, same way for F3. Three were sacrificed detection. SW-13 cells used clarify epigenetic molecular mechanism. Results This study confirmed activate glucocorticoid receptor ( GR ). activated , on one hand, up-regulated Let-7b (in human cells) inhibit steroidogenic acute regulatory protein StAR ) expression directly; other down-regulated CCCTC binding factor CTCF DNA methyltransferase 3a/3b Dnmt3a/3b ), resulting H19 hypermethylation low expression. decreased interaction let-7 can further steroidogenesis. Additionally, oocytes transmitted change H19/let-7c axis next rats. Due stability, F2 indirectly exposed also inhibited expression, be inherited F3 generation. Conclusions cascade effect CTCF/H19/Let-7c ultimately resulted transgenerational inheritance steroidogenesis inhibition offspring. deepens understanding intrauterine origin developmental toxicity, it will provide evidence systematic analysis acquired traits induced by PDE.

Language: Английский

Citations

3